Vasculogenesis and Angiogenesis in VEGF Receptor-1 Deficient Mice.
Vasculogenesis and Angiogenesis in VEGF Receptor-1 Deficient Mice.
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DOI：
10.1007/978-1-4939-2917-7_12
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Fong GH
中科院分区：
文献类型：
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作者：
Ho VC;Fong GH
血管内皮生长因子受体-1（VEGFR-1）/Flt-1是VEGF-A、VEGF-B和胎盘生长因子（PlGF）的跨膜酪氨酸激酶受体。VEGFR-1是一种神秘的分子，其在出生后血管生成中的确切作用仍存在争议。尽管许多出生后和成人研究已经通过操纵VEGFR-1配体进行，包括通过截短的VEGFR-1蛋白的竞争性结合，通过抗体的中和，或特异性配体过表达或敲除，但在受体本身的水平上，特别是在体内，知之甚少。令人困惑的是，尽管VEGFR-1在发育过程中负调控内皮细胞分化，但它在某些条件下在成人组织中，特别是在肿瘤和缺血组织中促进血管生成。此外，目前还不清楚VEGFR-1是如何参与血管成熟和维持血管静止在成人组织。为了便于进一步研究，我们产生了一个条件性敲除小鼠系VEGFR-1和特点的新生血管在出生后和成年小鼠，包括缺血心肌血管生成。我们在VEGF家族成员及其受体之间相互作用的背景下讨论了这些发现，并总结了VEGF途径中的各种小鼠模型。
Vascular endothelial growth factor receptor-1 (VEGFR-1)/Flt-1 is a transmembrane tyrosine kinase receptor for VEGF-A, VEGF-B, and placental growth factor (PlGF). VEGFR-1 is an enigmatic molecule whose precise role in postnatal angiogenesis remains controversial. Although many postnatal and adult studies have been performed by manipulating VEGFR-1 ligands, including competitive binding by truncated VEGFR-1 protein, neutralization by antibodies, or specific ligand overexpression or knockout, much less is known at the level of the receptor per se, especially in vivo. Perplexingly, while VEGFR-1 negatively regulates endothelial cell differentiation during development, it has been implied in promoting angiogenesis under certain conditions in adult tissues, especially in tumors and ischemic tissues. Additionally, it is unclear how VEGFR-1 is involved in vascular maturation and maintenance of vascular quiescence in adult tissues. To facilitate further investigation, we generated a conditional knockout mouse line for VEGFR-1 and characterized angiogenesis in postnatal and adult mice, including angiogenesis in ischemic myocardium. We discuss these findings in the context of the interplay between VEGF family members and their receptors, and summarize various mouse models in the VEGF pathway.